Analysis of Selective Androgen Receptor Modulators by Gas Chromatography-Microchip Atmospheric Pressure Photoionization-Mass Spectrometry

A gas chromatography-microchip atmospheric pressure photoionization-mass spectrometric (GC-μAPPI-MS) method was developed and used for the analysis of three 2-quinolinone-derived selective androgen receptor modulators (SARMs). SARMs were analyzed from spiked urine samples, which were hydrolyzed and derivatized with N-methyl-N-(trimethylsilyl)trifluoroacetamide before analysis. Trimethylsilyl derivatives of SARMs formed both radical cations (M+
• ) and protonated molecules ([M + H]+) in photoionization. Better signal-to-noise ratios (S/N) were obtained in MS/MS analysis using the M+
• ions as precursor ions than using the [M + H]+ ions, and therefore the M+
• ions were selected for the precursor ions in selected reaction monitoring (SRM) analysis. Limits of detection (LODs) with the method ranged from 0.01 to 1 ng/mL, which correspond to instrumental LODs of 0.2–20 pg. Limits of quantitation ranged from 0.03 to 3 ng/mL. The mass spectrometric response to the analytes was linear (R ≥ 0.995) from the LOQ concentration level up to 100 ng/mL concentration, and intra-day repeatabilities were 5%–9%. In addition to the GC-μAPPI-MS study, the proof-of-principle of gas chromatography-microchip atmospheric pressure chemical ionization-Orbitrap MS (GC-μAPCI-Orbitrap MS) was demonstrated.

Graphical AbstractA new application by GC-μAPPI-MS and a demonstration by GC-μAPCI-Orbitrap MS: Analysis of 2-quinolinone-derived selective androgen receptor modulators.Figure optionsDownload high-quality image (98 K)Download as PowerPoint slide